Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme (ACE) inhibitors have shown unexpected benefits in the prevention of ischemic events in patients with hypertension and congestive heart failure. In addition to these clinical observations, there is a growing body of knowledge about the molecular and cellular effects of ACE inhibitors. For example, ACE inhibition prevents stimulation of smooth muscle cell angiotensin II receptors, thereby blocking both contractile and proliferative actions. Angiotensin II blockade also diminishes the production of superoxide anion, which inactivates ambient nitric oxide. ACE inhibition of kininase II inhibits the breakdown of bradykinin, a direct stimulant of nitric oxide release from the intact endothelial cell. Thus, at the cellular level within the vasculature, ACE inhibition shifts the balance of ongoing mechanisms in favor of those promoting vasodilatory, antiaggregatory, antithrombotic, and antiproliferative effects. These effects underlie the potential benefits of ACE inhibition in the therapy of ischemia and atherosclerosis. Some data is available in humans to show that these effects can be sustained for months, thereby maintaining improved endothelial function and, presumably, allowing the initiation of steps that might alter the progression of atherosclerosis. Definitive information is not yet available in humans to show that ACE inhibition clearly alters the progression of atherosclerosis or diminishes coronary events in uncomplicated coronary disease. This promising area of investigation is, however, the subject of multiple clinical trials, which should provide clarification of this important question in coming years.
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PMID:Role of angiotensin-converting enzyme inhibition in reversal of endothelial dysfunction in coronary artery disease. 970 67

Combination therapy is a cost-effective and rational approach to treatment of severe hypertension and of mild to moderate hypertension that is refractory to monotherapy. The method has several advantages, most notably improved tolerability and enhanced antihypertensive efficacy. Long-term prospective studies are needed to confirm that such agents as calcium channel blockers, ACE inhibitors, and alpha 1 blockers reduce end-organ damage more effectively than do older antihypertensive drugs. However, scientific evidence strongly suggests that reducing risk factors for end-organ damage reduces heart, brain, kidney, and large-artery injury. Alpha 1 blockers appear to be a particularly suitable choice for use in combination regimens. The only class of agents that should be avoided in combination with alpha 1 blockers is central alpha agonists; all other agents act in an additive or synergistic fashion. Unlike diuretics and beta blockers, alpha 1 blockers do not adversely affect serum lipid, glucose, or insulin levels. In fact, alpha 1 blockers may improve these measurements and also counteract the adverse effects of other antihypertensive agents on them. Alpha1-blocker therapy may bring about regression of LVH, and it does not have deleterious effects on disorders that often coexist with hypertension (e.g., gout, chronic obstructive lung disease, peripheral ischemia).
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PMID:Alpha 1-blocker combination therapy for hypertension. 974 10

Aberrations in cell Ca2+ homeostasis have been known to parallel both changes in membrane lipid composition and aging. Previous work has shown that the lowered efficiency of work performance, which occurs in isolated hearts from rats fed a diet rich in n-6 polyunsaturated fatty acids (PUFA), relative to those fed n-3 PUFA, could be raised by mitochondrial (Mito) Ca2+ transport inhibition. We tested whether, after Ca2+-dependent stress, the Ca2+-dependent activation of pyruvate dehydrogenase (PDHA/PDHTotal) and Mito Ca2+ cycling could be manipulated by varying the ratio of n-3 to n-6 PUFA in Mito membranes in young (6 mo) and aged (24 mo) isolated rat hearts treated to n-3 or n-6 PUFA-rich diet. Inotropic stimulation by 1 microM norepinephrine (NE) of 24-mo n-6 PUFA-rich hearts elevated total Mito Ca2+ content 38% more than in 6-mo hearts (P < 0. 05). However, both the NE-induced rise in Mito Ca2+ and the difference in response between 6- and 24-mo hearts were partially abolished by n-3 PUFA treatment. NE increased the fractional activation of PDH by 44% above control levels in the 6-mo group compared with 49% in the 24-mo group after n-6 PUFA diet. However, NE stimulation of PDHA was attenuated by n-3 PUFA diet, attaining values only 29 and 23% above control levels in 6- and 24-mo mitochondria, respectively (P < 0.05). Global ischemia and reperfusion (I/R) in n-6 PUFA hearts gave rise to higher levels of total Mito Ca2+ concentration (P < 0.0001) and PDHA (P < 0.0001) compared with n-3 PUFA. Ruthenium red (3.4 microM) abolished the effects of I/R in all groups. With aging, heart Mito membrane phosphatidylcholine was increased after n-6 PUFA-rich diet (by approximately 15%, P < 0.05), whereas cardiolipin and n-3 PUFA content were diminished by 31% (P < 0.05) and 73% (P < 0.05), respectively. These effects were prevented by n-3 PUFA-rich diet. The present study, by directly manipulating the cardiac Mito membrane n-3-to-n-6 PUFA ratio, shows that the activation of Ca2+-dependent PDH can be augmented when the n-3-to-n-6 PUFA ratio is low (n-6 PUFA-rich diet; 24-mo hearts) or attenuated when this ratio is relatively high (n-3 PUFA-rich diet). We propose that one of the consequences of dietary-induced manipulation of membrane phospholipids and PUFAs may be the altered flux of Ca2+ across the Mito membrane and thus altered intramitochondrial Ca2+-dependent processes.
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PMID:PUFA and aging modulate cardiac mitochondrial membrane lipid composition and Ca2+ activation of PDH. 988 28

Preventing the progression of established heart failure can be difficult, as multiple factors contribute to the continual decline of cardiac function. Blunting the activated neurohormonal response to a decreased systolic function is a proven means of slowing progression of CHF. Preventing further CAD and cardiac ischemia may also prove to be an effective mechanism. Two trials with HMGCoA reductase inhibitors lend support to this hypothesis. Studies using ACE inhibitors may also support this notion. Since a major portion of heart failure in the USA is caused by CAD, preventing CHF progression may be related to the prevention of CAD. Using ACE inhibitors and lipid-lowering agents, in addition to standard measures of CAD risk factor modification, may prove useful in future trials to retard the progression of heart failure. Further research and clinical trials involving this method of CHF prevention are warranted.
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PMID:Role of secondary prevention in congestive heart failure due to coronary artery disease. 989 17

Kinins have been shown to play an important role in the cardioprotective effect of ACE inhibitors (ACEi) during heart failure and ischemia-reperfusion. However, it is controversial as to whether kinins oppose the hypertensinogenic effect of deoxycorticosterone acetate plus salt (DOCA-salt) or aortic coarctation and whether they mediate both chronic antihypertensive and cardiac antihypertrophic effects of ACEi in hypertension. Using normal 129/SvEvTac mice and mice lacking the bradykinin B2 receptor gene (B2-KO), we investigated whether (1) the hypertensinogenic effect of DOCA-salt or aortic coarctation is enhanced in B2-KO mice and (2) the chronic antihypertensive and antihypertrophic effects of an ACEi (ramipril, 4 mg. kg-1. d-1) are mediated by B2 receptors in aortic coarctation (6 weeks)- and DOCA-salt (4 weeks)-induced hypertension. Before surgery, there was no difference between 129/SvEvTac and B2-KO mice in terms of blood pressure and heart weight, suggesting that kinins are not essential to maintaining normal blood pressure. DOCA-salt (volume expansion) or aortic coarctation (renin-dependent) induced similar hypertension and left ventricular hypertrophy (LVH) in 129/SvEvTac and B2-KO mice, suggesting that kinins do not play an essential role in the development of DOCA-salt- or aortic coarctation-induced hypertension. We found that B2 receptors mediate only the early (1 week) but not the late phase (4 weeks) of the chronic hypotensive effect of ACEi in DOCA-salt hypertension. On the other hand, chronic ACE inhibition prevented the development of hypertension and LVH in both 129/SvEvTac and B2-KO mice given DOCA-salt or subjected to aortic coarctation, suggesting that kinins do not participate in the chronic antihypertensive and antihypertrophic effects of ACEi in these 2 models of hypertension. Thus, in mice, kinins acting via B2 receptors do not participate in (1) maintenance of normal basal blood pressure, (2) establishment and maintenance of hypertension induced by DOCA-salt or aortic coarctation, and (3) chronic antihypertensive and cardiac antihypertrophic effects of ACEi in DOCA-salt and aortic coarctation hypertension.
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PMID:Effect of ACE inhibitor on DOCA-salt- and aortic coarctation-induced hypertension in mice: do kinin B2 receptors play a role? 1060 Nov 37

Nitrates have been widely used in the treatment of patients with chronic congestive heart failure. Although the use of these drugs has not been approved by the Food and Drug Administration, multiple studies have shown their favorable effects. Organic nitrates have been shown to have a beneficial effect on ischemia, hemodynamic profile, magnitude of a mitral regurgitation, endothelial function, and cardiac remodeling. These drugs, when used in combination with hydralazine, have improved exercise capacity and survival. Recent studies have shown that the use of nitrates in patients already treated with standard heart failure therapy, including angiotensin converting enzyme (ACE) inhibitors, resulted in hemodynamic improvement, marked enhancement of exercise tolerance, reduction of left ventricular size, and augmentation of systolic function. These data suggest a role for organic nitrates as an adjunctive therapy to ACE inhibitors in patients with chronic heart failure and for nitrates in combination with hydralazine as an alternative treatment in patients who are intolerant to ACE inhibitors.
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PMID:The role of organic nitrates in the treatment of heart failure. 1036 48

ANP model in rats was used to determine the concentration of TXB2, PGF1 alpha in plasma and the ACE activity in serum in five groups. The concentration of TXB2, PGF1 alpha in all experimental groups was significantly different from that of control group (P < 0.05). The comparison of ACE activity was just the same as the above except that of 6 h. The factors leading to pancreatic ischemia functioned continously. We conclude that pancreatic ischemia is a continuous injury factor in ANP, and there is no reperfusion-injury in the course of the disease.
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PMID:[Pancreatic ischemia: a continuous injury factor in acute necrotic pancreatitis]. 1037 21

The cerebral blood flow (CBF) is autoregulated to a steady flow within certain ranges. CBF increases and cerebrovascular resistance (CVR) decreases dramatically with breakthrough of autoregulation when systemic arterial blood pressure exceeded the upper limit of the range. Many kinds of components in the brain as well neurogenic factors affect the autoregulation. The breakthrough of autoregulation does not occur in the presence of nitric oxide (NO) synthesis inhibitors, angiotensin converting enzyme inhibitor, prostanoids (PG) administered in the brain, sympathetic denervation, and sinoaortic denervation. The abolishment of breakthrough of autoregulation may be due to an increased tolerance of cerebral vessels to hypertension and the inhibition of the release of a vasodilator substance such as NO or PG. It appears that the tone of brain microvessels is controlled towards dilation by cholinergic innervation originating from the nucleus basalis of Meynert, glutamatergic or GABAergic mediated GABAA receptor, and by a mediator such as NO, bradykinin, PGs. Also, it is likely that candidates for constricting factors in intraparenchymal microvessels are norepinephrinergic from the superior cervical ganglion, serotonergic involved in 5-HT1D beta- and 5-HT2B-specific receptor subtypes, GABAergic mediated GABAB receptor, thromboxane, PG F2 alpha and the angiotensin system. The autoregulation of CBF is maintained by these neurogenic factors to prevent brain ischemia and hyperemia.
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PMID:[Microcirculation in the brain: viewpoint of autoregulation]. 1041 58

Hypertension is a significant and prevalent risk factor for the development of cardiovascular disease and target organ damage. The urgency of treatment of high blood pressure depends on the level of blood pressure elevation and the presence of coexistent risk factors for cardiovascular disease. Likewise, the level to which blood pressure is reduced is not restricted to the definition of high blood pressure but instead depends on the underlying disease. Diabetes and renal insufficiency, for example, require blood pressure goals below those that are traditionally defined. In the absence of contraindications, beta-blockers and diuretics are still recommended as first-line agents for treatment of uncomplicated hypertension. Calcium channel antagonists also may reduce mortality. In patients with diabetes, ACE inhibitors are effective first-line agents in type 1 and type 2 diabetic patients who are hypertensive or have microalbuminuria. ACE inhibitors may be beneficial in patients with nondiabetic renal insufficiency as well. Calcium channel antagonists may have some effect in retarding progression of diabetic nephropathy although a recent trial found a higher incidence of death as a secondary endpoint in hypertensive diabetic patients who were treated with calcium channel antagonists. Beta-blockers seem to be safe and well tolerated in patients with mild to moderate intermittent claudication, although patients with rest pain or limb ischemia have not been studied. Beta-blockers should not be used in patients with asthma. Dihydropyridine calcium channel antagonists are the preferred treatment of hypertension in patients with Raynaud's but should be avoided in patients with severe gastroesophageal reflux disease. NSAIDs, particularly piroxicam and indomethacin, raise mean blood pressure by approximately 5 mm Hg, enough to consider a change of either NSAID or antihypertensive to one that is not as affected by NSAIDs. Cyclosporine A can induce hypertension by its vasoconstrictive effects, particularly on the kidney. Calcium channel antagonists may antagonize this vasoconstriction while allowing the clinician to reduce the dose of cyclosporine A required to achieve its immunosuppressive effect.
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PMID:Evaluation and treatment of hypertension. 1046 27

Regional left ventricular contractility caused by myocardial stunning as a result of transient ischemia and postreperfusion injury is a reversible state it can however persist even for several month. It seems reasonable to shorten this period as much as possible. The aim of the study was to estimate the influence of treatment with metoprolol or enalapril on the recovery of contractile function of left ventricle in patients after acute myocardial infarction treated thrombolytically. Investigations were carried out in 127 patients (mean age 62.3 +/- 11.9 years). Metoprolol was used in 37 patients in dose 0.02-0.05 g b.i.d., enalapril in 48 patients 0.0025-0.01 g b.i.d. 42 patients were not treated with any beta-blocker or ACE inhibitor. In all patients echocardiographic study was performed 3 times: on 2-3rd day following acute myocardial infarction immediately before introducing the treatment with metoprolol or enalapril, after 1 month and after 3 months. Echocardiographic study wall motion index (WMI) was calculated basing on. Significant decrease in WMI was observed after 1 month compared to its value on 2-3rd day acute myocardial infarction and after 3 months compared to 1 month after myocardial infarction in each of 3 subgroups of patients. No statistically significant differences in WMI were found out between studied subgroups. Neither metoprolol nor enalapril started on 2-3rd after thrombolytic treatment of acute myocardial infarction do not affect the recovery of contractile function of stunned myocardium.
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PMID:[Influence of treatment with metoprolol or enalapril on recovery of contractile function of the left ventricle in patients after acute myocardial infarction treated by thrombolytics]. 1052 15


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